FDA Sat on Report Linking Suicide, Drugs

Although drug trials have yet to show efficacy for most of the drugs in children, many doctors and patients think that they help depressed kids, FDA officials said.

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Expert's Results Differ

Mosholder was assigned in June to head up the FDA's assessment of a possible association between Paxil and suicidal behavior in children, but his mandate was broadened to include other antidepressants. By January he had come up with conclusions that did not jibe with the FDA's official position, according to internal FDA e-mails and interviews with FDA officials other than Mosholder.

The FDA's official public position was that there was not adequate data to support a link between antidepressants and possible suicide.

At first, FDA officials had planned to have Mosholder tell the advisory panel about his conclusions. One of the internal documents was a trial question-and-answer session, rehearsing what Mosholder would tell the committee. In italic type, Mosholder was asked questions about his analyses and coached on how he should handle them.

Mosholder's answers, summarizing his findings, appeared in normal type.

Mosholder wrote that trials of eight antidepressant drugs, involving 4,100 pediatric patients, showed 108 suicide-related events -- 74 on drugs and 34 on placebo.

About a quarter of the events could be classified as serious; and most of the suicide-related events were among children suffering major depressive disorder, not from the other diseases treated with the medications, such as obsessive-compulsive disorder. In these seriously depressed patients, there was one serious suicide-related event per five patient years on the drug, compared with one per 10 patient years on the drug for placebos. Patient years are a statistical measure of the frequency of drug side effects.

Mosholder also wrote that the risk was most evident for paroxetine, or Paxil, and venlafaxin, or Effexor. His findings also suggested that patients should not quickly stop taking the drugs. About a quarter of the suicide-related events on paroxetine occurred within four days of discontinuing the drug, he wrote.

In italics, Mosholder was advised not to give any recommendations to the panel and to acknowledge the limitations of his analyses "relative to the definitive analyses being prepared."

Later, senior officials decided Mosholder should not appear before the advisory committee, and it was not told of his work